Dynamics of fertility impairment and recovery after allogeneic haematopoietic stem cell transplantation in childhood and adolescence: results from a longitudinal study

Pfitzer, Constanze; Orawa, Helmut; Balcerek, Magdalena; Langer, Thor﻿s﻿ten; Dirksen, Uta; Keslová, Petra; Zubarovskaya, Natalia; Schuster, Friedhelm R.; Jarisch, Andrea; Strauß, Gabriele; Borgmann‐Staudt, Anja

doi:10.1007/s00432-014-1781-5

Cited by 40 publications

(43 citation statements)

References 18 publications

(29 reference statements)

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“…Of particular importance is the effect on fertility. It is well established in murine and human studies that both myeloablative and nonmyeloablative doses of busulfan may impact fertility [8,9,46]. Much less information exists on the gonadal toxicities of treosulfan.…”

Section: Discussionmentioning

confidence: 99%

Bone Marrow Transplantation after Nonmyeloablative Treosulfan Conditioning Is Curative in a Murine Model of Sickle Cell Disease

Devadasan

Sun

Westin

et al. 2018

Biology of Blood and Marrow Transplantation

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Allogeneic hematopoietic stem cell transplantation (HSCT) can be curative for patients with sickle cell disease (SCD). However, morbidity associated with myeloablative conditioning and graft-versus-host disease has limited its utility. To this end, autologous HSCT for SCD using lentiviral gene-modified bone marrow (BM) or peripheral blood stem cells has been undertaken, although toxicities of fully ablative conditioning with busulfan and incomplete engraftment have been encountered. Treosulfan, a busulfan analog with a low extramedullary toxicity profile, has been used successfully as part of a myeloablative conditioning regimen in the allogeneic setting in SCD. To further minimize toxicity of conditioning, noncytotoxic monoclonal antibodies that clear stem cells from the marrow niche, such as anti-c-Kit (ACK2), have been considered. Using a murine model of SCD, we sought to determine whether nonmyeloablative conditioning followed by transplantation with syngeneic BM cells could ameliorate the disease phenotype. Treosulfan and ACK2, in a dose-dependent manner, decreased BM cellularity and induced cytopenia in SCD mice. Conditioning with treosulfan alone at nonmyeloablative dosing (3.6 g/kg), followed by transplantation with syngeneic BM donor cells, permitted long-term mixed-donor chimerism. Level of chimerism correlated with improvement in hematologic parameters, normalization of urine osmolality, and improvement in liver and spleen pathology. Addition of ACK2 to treosulfan conditioning did not enhance engraftment. Our data suggests that pretransplant conditioning with treosulfan alone may allow sufficient erythroid engraftment to reverse manifestations of SCD, with clinical application as a preparative regimen in SCD patients undergoing gene-modified autologous HSCT.

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Section: Discussionmentioning

confidence: 99%

Bone Marrow Transplantation after Nonmyeloablative Treosulfan Conditioning Is Curative in a Murine Model of Sickle Cell Disease

Devadasan

Sun

Westin

et al. 2018

Biology of Blood and Marrow Transplantation

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“…Furthermore, specific information on the effect of treatment with total body irradiation or conditioning chemotherapy required before haematopoietic stem cell transplantation is limited, which is a key part of treatment for some leukaemias. Worryingly initial evidence shows a fertility impairment in 57% of exposed females after a median time of 2.3 years after haematopoietic stem cell transplantation (Pfitzer et al, 2015).…”

Section: Fertility After Leukaemiamentioning

confidence: 99%

Fertility in female cancer survivors: a systematic review and meta-analysis

Busnelli

Vitagliano

Mensi

et al. 2020

Reproductive BioMedicine Online

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“…The serious damage to the gonads in both sexes leads to a high risk of permanent infertility. [6][7][8] A study from 199…”

Section: Introductionmentioning

confidence: 99%

A prospective study on the long‐term outcome of prepubertal and pubertal boys undergoing testicular biopsy for fertility preservation prior to hematologic stem cell transplantation

Borgström

Fridström

Gustafsson

et al. 2020

Pediatric Blood & Cancer

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Background Few studies have reported the long‐term outcomes of prepubertal and pubertal boys undergoing testicular biopsy for fertility preservation (FP). Procedure This prospective longitudinal study examined 21 boys (aged 1.5‐14.5 years) who underwent testicular biopsy for FP prior to allogeneic (n = 20) or autologous (n = 1) hematological stem cell transplantation (HSCT) between 2003 and 2010. During counseling, pubertal boys were encouraged to produce a sperm sample by masturbation , while prepubertal boys were presented with surgical testicular tissue retrieval as an option for experimental FP. Clinical outcomes included postoperative complications, pubertal development, and sex‐hormone levels. Survivors approaching adulthood were encouraged to provide semen samples. Results Twenty boys, including 14 in prepuberty and six in early puberty (Tanner stage 2‐3), underwent open testicular biopsies. Two pubertal biopsies contained mature sperms, which were cryopreserved. Testicular tissue was vitrified in the remaining 18 cases. One pubertal boy (Tanner stage 4) underwent percutaneous testicular sperm aspiration and sperms obtained were cryopreserved. Postoperative complications (hematoma or infection) were rare. Overall, 14 boys survived >5 years (mean follow‐up after HSCT, 7.2 years) and 11 showed advanced puberty. Semen samples were provided by five boys and obtained sperm were cryopreserved from two. Individuals at adulthood had normal testosterone levels but subnormal testicular size, high follicle stimulating hormone, and low inhibin B and anti‐Müllerian hormone levels. Conclusion No long‐term risks were detected during continuous clinical follow‐up. Experimental testicular biopsies for FP were well accepted by the patients and families, despite the absence of methods to use prepubertal tissue for fertility treatment.

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Dynamics of fertility impairment and recovery after allogeneic haematopoietic stem cell transplantation in childhood and adolescence: results from a longitudinal study

Abstract: In the light of the dynamics of fertility impairment and recovery in the HSCT patients reviewed, these patients should be counselled comprehensively regarding fertility preservation measures.

Cited by 40 publications

References 18 publications

Bone Marrow Transplantation after Nonmyeloablative Treosulfan Conditioning Is Curative in a Murine Model of Sickle Cell Disease

Bone Marrow Transplantation after Nonmyeloablative Treosulfan Conditioning Is Curative in a Murine Model of Sickle Cell Disease

Fertility in female cancer survivors: a systematic review and meta-analysis

A prospective study on the long‐term outcome of prepubertal and pubertal boys undergoing testicular biopsy for fertility preservation prior to hematologic stem cell transplantation

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